Hepatotoxicity Clinical Research Network

肝毒性临床研究网络

• 批准号: 6949008
• 负责人: TIMOTHY J DAVERN
• 金额: $ 18.18万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6949008
• 关键词: HIV infections; alternative medicine; clinical research; cooperative study; drug adverse effect; genetic polymorphism; hepatotoxin; human genetic material tag; human subject; liver toxic disorder; liver transplantation; medical outreach /case finding; patient /disease registry; tissue resource /registry; tuberculosis

DESCRIPTION (provided by applicant): Hepatotoxicity, or drug-induced liver inury (DILl), is currently the most common cause of fulminant hepatic failure in the United States and the main indication for market withdrawal of drugs and, thus, it is a problem of enormous medical, financial, legal and regulatory importance. Although a vast number of drugs, toxins and alternative medications have the potential to cause hepatotoxcity, severe DILl is a problem of sufficient rarity that a large group of dedicated investigators working in a coordinated effort will be required to better understand the pathogenesis of DILl and develop effective prevention and treatment strategies. This proposal brings together a unique, multi-disciplinary consortium of investigators and resources, concentrated within Northern California but also including sites across the country, with a plan for a participating Clinical Center in the Hepatotoxicity Clinical Research Network (HCRN). Our research plan describes, firstly, the establishment of a large multicomponent Clinical Center patient database that would contribute to the proposed multicenter HCRN. The proposed DILl patient informational database, serum, DNA and tissue bank will comprise a prospective cohort derived from several sources, each providing distinct epidemiological facets and research potential. These include the Liver Transplant Programs at UCSF, Stanford University and California Pacific Medical Center, the Tuberculosis Clinics at San Francisco General Hospital, Boston University, Emory University, University of Puerto Rico, and Louisiana Health Sciences Center, and the HIV Clinic at San Francisco General Hospital. At each site, we have developed strategies to identify well-defined cases of toxin-induced liver injury in a prospective manner that will permit careful collection of detailed epidemiological and clinical information, as well as serum, DNA and tissue samples for biochemical, pharmacological and genetic studies. We plan to initially identify patients with potential DILl based on proposed operational diagnostic criteria and then further evaluate cases using a validated causality assessment instrument. Patients classified as having "highly probable" DILl using this instrument will be followed prospectively in order to better define the natural history of DILl. Identification of such DILl-associated polymorphisms is an essential first step in the development of a rational gene-based prevention strategy. We anticipate that our Clinical Center will recruit approximately 120 cases and well-matched controls from an ethnically and racially diverse patient population to the national HCRN network. We have a well-organized, multi-disciplinary group of physicians, scientists, and research nurses who are dedicated to the success of this Clinical Center and the overall National Hepatoxicity Clinical Research Network.

描述（由申请人提供）： 目前，肝毒性或药物引起的肝脏（DILL）是美国暴发性肝衰竭的最常见原因，也是市场戒断药物的主要迹象，因此，这是巨大的医疗，财务，法律，法律和法规重要性的问题。尽管大量药物，毒素和替代药物具有引起肝毒性的潜力，但严重的莳萝是一个足够稀有性的问题，即需要大量专门的研究人员从事协调努力的工作，才能更好地了解DILL的发病机理并制定有效的预防和治疗策略。该提案汇集了一个独特的，多学科的研究人员和资源联盟，集中在北加州，但还包括全国各地的地点，并计划在肝毒性临床研究网络（HCRN）中建立参与临床中心。我们的研究计划首先描述了建立大型多组分临床中心患者数据库，该数据库将有助于拟议的多中心HCRN。拟议的DILL患者信息数据库，血清，DNA和组织库将构成源自多个来源的前瞻性队列，每个来源都提供不同的流行病学方面和研究潜力。其中包括UCSF，斯坦福大学和加利福尼亚太平洋医学中心的肝移植计划，旧金山综合医院的结核病诊所，波士顿大学，埃默里大学，波多黎各大学和路易斯安那大学健康科学中心以及HIV诊所的HIV诊所。在每个地点，我们都制定了策略，以预期的方式鉴定毒素诱导的肝损伤的良好情况，这将允许仔细收集详细的流行病学和临床信息，以及血清，DNA和组织样品，以进行生化，药理和遗传学研究。我们计划根据提议的操作诊断标准最初鉴定具有潜在DILL的患者，然后使用经过验证的因果关系评估工具进一步评估病例。前瞻性地遵循被归类为使用该仪器的“高度可能”莳萝的患者，以更好地定义莳萝的自然历史。鉴定这种莳萝相关的多态性是发展基于理性基因的预防策略的重要第一步。我们预计，我们的临床中心将招募大约120例病例，并从种族和种族多样化的患者人群到国家HCRN网络匹配。我们有一个组织良好的，多学科的医师，科学家和研究护士组，他们致力于该临床中心和整个国家肝脏临床研究网络的成功。